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The self-stress sensing response of smart ultra-high-performance concrete (S-UHPC) under high cyclic compressive stress was investigated at different temperatures between 15 °C and 35 °C as a basic study for understanding the effects of temperature on the self-stress sensing response of S-UHPC. The S-UHPC has maintained the quasi-linear relationship between stress and fractional change in electrical resistivity (FCR) even under cyclic stress. The stress-sensing coefficient (SSC) of S-UHPC almost linearly decreased from 0.2450 %/MPa to 0.1722%/MPa with increasing the temperature from 15 °C to 35 °C. The lower SSC at higher temperature is based on the decreased electrical resistivity (∆ρ) of S-UHPCs owing to more activated ion movements in S-UHPCs.

Background: Worldwide, children are increasingly being diagnosed with autism spectrum disorder (ASD). The case of South Korea is not exceptional. One of the core symptoms of children with ASD is sensory reactivity issues, such as an unusual interest in the sensory aspects of the environment. One promising development in sensory enrichment for individuals with ASD is a multisensory environment (MSE).Objectives: This study investigated the influence of MSE on the target behaviors of children with ASD with different sensory characteristics in the case of South Korea.Methods: A multiple treatment design {A-B-C-D (B + C) phases} was implemented to observe the six target behaviors of three children with ASD. The sensory environmental intervention focusing on visual and auditory stimuli was manipulated as a stimulating MSE or a relaxing MSE depending on the sensory profile of each participant. The analysis was undertaken using visual inspection with data patterns and graph slopes, which is a customary method of analyzing the single-subject design data. In addition, the means and standard deviations of the two target behaviors of each participant were analyzed together.Results: The findings reveal that MSE interventions positively affected the target behaviors of children with ASD with diverse sensory characteristics. The stimulating MSE created by the integration of visual and auditory stimuli was the most effective intervention for the participants with hypo-visual and hypo-auditory sensitivities in this study.Conclusions: The MSE could be meaningful as a nonpharmaceutical therapy that could influence the daily behaviors of children with ASD.

In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). MBs were prepared via the photo-crosslinking of bisphosphonate (alendronate)-conjugated methacrylated HA (Alen-MHA). The polyanionic Alen-MHA MBs actively absorbed cationic BMP2 up to 91.0% of the loading efficacy and displayed a sustained release of BMP2 for 10 days. BMP2/Alen-MHA MBs induced osteogenic-related genes in cellular experiments and showed the highly increased bone formation efficacy in thigh muscle injection and rat spinal fusion animal models. Thus, BMP2/Alen-MHA MBs provide a promising opportunity to improve the delivery efficiency of BMP2.

IMPORTANCE: There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. OBJECTIVE: To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. DESIGN, SETTING, AND PARTICIPANTS: This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. EXPOSURES: Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription–polymerase chain reaction. MAIN OUTCOMES AND MEASURES: Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. RESULTS: A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days; P = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. CONCLUSIONS AND RELEVANCE: In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n= 129 (67.9%); VTD6, n= 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P< 0.001), but, the pre- and post-ASCT ≥ very good partial response (VGPR), and 2-year PFS were similar. Multivariate analysis revealed age, β2-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P= 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P= 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.

Backgroud:Waldenström macroglobulinemia (WM) is an indolent B-cell malignancy characterized by the presence of immunoglobulin M (IgM) monoclonal gammopathy and lymphoplasmacytic bone marrow infiltration. Recently, the superior efficacy of BTK inhibitors and other novel agents has been established. However, BTK inhibitors has been shown limited efficacy in patients with CXCR4 mutation and MYD88 wild type. Therefore, the importance of chemotherapy which do not contain BTK inhibitors still remain. This study was conducted to estimate the efficacy and safety of the combination of rituximab, bortezomib, lenalidomide and dexamethasone in patients with WM in South Korea.

Introduction

In a previous study (SY Ahn et al, Cancer Res Treat 2023), we reported that the presence of only the basic leucine zipper in-frame mutation (bZIP in-f) CEBPAis associated with favorable outcomes in patients with CEBPAdouble mutations. However, when bZIP in-fCEBPAmutations were accompanied by certain mutations in chromatic/DNA modifiers, cohesion complex, and splicing genes, patients exhibited inferior overall survival (OS). FLT3-ITD or additional cytogenetic abnormalities is known to rarely co-occur with CEBPAmutation in patients with AML. In cases where both bZIP in-fCEBPAand FLT3-ITD coexist, there are conflicting aspects in risk stratification, and research on its prognostic significance is limited. Therefore, we aimed to evaluate the prognostic significances of the co-occurrence of bZIP in-fCEBPAmutation with unfavorable genetic abnormalities in acute myeloid leukemia.

Previous retrospective studies have revealed that a substantial portion of PV patients experience resistance to hydroxyurea (HU-R) and intolerance to HU (HU-I). Currently, the therapeutic options for both groups of patients do not differ, and most clinical trials investigating second-line therapies have enrolled patients with HU-R or HU-I without considering potential clinical distinctions between the two groups. Direct comparisons between patients with HU resistance and HU intolerance have not been conducted, and prognostic factors related to clinical outcomes, such as thrombosis, bleeding, disease progression, and survival, remain unclear for patients experiencing HU resistance or intolerance.

In sacrococcygeal teratoma, the presence of high‐output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N‐terminal pro‐B‐type natriuretic peptide [NT‐pro‐BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT‐pro‐BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3/cm, elevated NT‐pro‐BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf’s antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model.

UV radiation decreases type I procollagen production mainly by inhibiting the transforming growth factor-β/Smad signaling pathway. Because further epigenetic regulatory mechanisms are unclear, we investigated the roles of DNA methylation and histone acetylation in UV-induced regulation of COL1A2transcription in human dermal fibroblasts. Anacardic acid, a p300 histone acetyltransferase inhibitor, rescued the UV-induced decrease of type I procollagen expression in human dermal fibroblasts. Although UV irradiation induced global histone acetylation, it reduced the local recruitment of histone H3 acetylation as well as p300, and Smad2/3 to the p300 binding site (-1406/-1393), in the COL1A2promoter as shown by chromatin immunoprecipitation. This effect was reversed by anacardic acid treatment. In contrast, pyrosequencing analysis showed that UV irradiation induced DNA methylation in the same region of the COL1A2promoter, which was reversed by anacardic acid and a DNA methyltransferase inhibitor (5-AZA-2′-deoxycytidine). Inhibition of UV-induced DNA methylation led to an increase of UV-induced histone acetylation in the COL1A2promoter and increased the recruitment of transcription factors, leading to up-regulation of type I collagen after UV irradiation. Collectively, our findings indicate that the epigenetic crosstalk between DNA methylation and histone acetylation plays a crucial role in COL1A2transcription induced by UV irradiation.

This retrospective study compared the mortality and short-term complications according to the choice of general anesthesia or regional anesthesia in patients who underwent a total knee arthroplasty (TKA). We searched the Korean National Health Insurance Service National Sample Cohort database to analyze data from patients who received a TKA between January 2002 and December 2015. Before comparing the general and the regional anesthesia groups, the bias was reduced by propensity score matching. After matching, the mortality and complications occurring within 30 days after a TKA were compared between the 2 groups. In the database, 6491 primary TKA cases were identified. Nine hundred forty-three patients (14.5%) had a TKA performed under general anesthesia, and 5548 (85.5%) had a TKA performed under regional anesthesia. After propensity score matching, the data of 1886 patients were analyzed, with 943 patients in each group. There was no significant difference in mortality (0.32% vs 0.00%), transfusion rate (84.52% vs 84.73%, P= .8989), and length of hospital stay (50 vs 53, P= .5391) between the general and regional anesthesia groups. Most of the complications were not significantly different, but the major complications, including myocardial infarction (1.70% vs 0.64%, P= .0414) and acute renal failure (0.85% vs 0.11%, P= .0391), were higher in the general anesthesia group than in the regional anesthesia group. Also, admission to the intensive care unit (8.48% vs 2.33%, P< .0001) and total cost (₩8067, 400 vs ₩7487, 940, P= .0002) were higher in the general anesthesia group than in the regional anesthesia group. Our study found that regional anesthesia for TKA is associated with a decrease in major complications, including myocardial infarction and acute renal failure, and medical costs.

This study investigates the effect of input current direction on the electrical voltages of ultra-high-performance concrete containing fine steel slag aggregates (UA). For the application of electrical impedance tomography based on Laplace’s equation, electrical voltage should be identical under different input current directions. However, the electrical voltages of UA differ significantly corresponding to forward and backward current directions. The percentage differences of real voltages (VRE¯) corresponding to different input current directions are between 4.57 and 76.39% under different boundary conditions such as Wenner, same-boundary, and opposite-boundary conditions. VRE¯originates from a different internal resistance of the internal path (Rip) corresponding to the input current direction. Among the investigated boundary conditions, the Wenner boundary condition provides the lowest VRE¯because it leads to the generation of an almost uniform current density between the two inner probes used for measuring voltages than other conditions.

Cancer stem cells (CSCs) are resistant to chemo- and radio-therapy, and can survive to regenerate new tumors. This is an important reason why various anti-cancer therapies often fail to completely control tumors, although they kill and eliminate the bulk of cancer cells. In this study, we determined whether or not adenine nucleotide translocator-2 (ANT2) suppression could also be effective in inducing cell death of breast cancer stem-like cells. A sub-population (SP; CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. We utilized the adeno-ANT2 shRNA virus to inhibit ANT2 expression and then observed the treatment effect in a SP of breast cancer cell line. In this study, MCF7, MDA-MB-231 cells, and breast epithelial cells (MCF10A) mesenchymally-transdifferentiated through E-cadherin knockdown were used. ANT2 expression was high in both stem-like cells and non-stem-like cells of MCF7 and MDA-MB-231 cells, and was induced and up-regulated by mesenchymal transdifferentiation in MCF10A cells (MCF10AEMT). Knockdown of ANT2 by adeno-shRNA virus efficiently induced apoptotic cell death in the stem-like cells of MCF7 and MDA-MB-231 cells, and MCF10AEMT. Stem-like cells of MCF7 and MDA-MB-231, and MCF10AEMTcells exhibited increased drug (doxorubicin) resistance, and expressed a multi-drug resistant related molecule, ABCG2, at a high level. Adeno-ANT2 shRNA virus markedly sensitized the stem-like cells of MCF7 and MDA-MB-231, and the MCF10AEMTcells to doxorubicin, which was accompanied by down-regulation of ABCG2. Our results suggest that ANT2 suppression by adeno-shRNA virus is an effective strategy to induce cell death and increase the chemosensitivity of stem-like cells in breast cancer.

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2 per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2 per day times 3 days) in addition to cytarabine (200 mg/m2 per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.

We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m2per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m2per day times 3 days) in addition to cytarabine (200 mg/m2per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P= .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P= .030; EFS, 40.8% vs 28.4%, P= .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P= .024; OS, HR, 0.739, P= .032; EFS, HR, 0.774, P= .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.govas #NCT00474006.

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin-shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.

The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.

Oxidized LDL (OxLDL), a causal factor in atherosclerosis, induces the expression of heat shock proteins (Hsp) in a variety of cells. In this study, we investigated the role of CD36, an OxLDL receptor, and peroxisome proliferator-activated receptor ? (PPAR?) in OxLDL-induced Hsp70 expression. Overexpression of dominant-negative forms of CD36 or knockdown of CD36 by siRNA transfection increased OxLDL-induced Hsp70 protein expression in human monocytic U937 cells, suggesting that CD36 signaling inhibits Hsp70 expression. Similar results were obtained by the inhibition of PPAR? activity or knockdown of PPAR? expression. In contrast, overexpression of CD36, which is induced by treatment of MCF-7 cells with troglitazone, decreased Hsp70 protein expression induced by OxLDL. Interestingly, activation of PPAR? through a synthetic ligand, ciglitazone or troglitazone, decreased the expression levels of Hsp70 protein in OxLDL-treated U937 cells. However, major changes in Hsp70 mRNA levels were not observed. Cycloheximide studies demonstrate that troglitazone attenuates Hsp70 translation but not Hsp70 protein stability. PPAR? siRNA transfection reversed the inhibitory effects of troglitazone on Hsp70 translation. These results suggest that CD36 signaling may inhibit stress-induced gene expression by suppressing translation via activation of PPAR? in monocytes. These findings reveal a new molecular basis for the anti-inflammatory effects of PPAR?.

Karyotypic abnormalities in cultured embryonic stem cells (ESCs), especially near-diploid aneuploidy, are potential obstacles to ESC use in regenerative medicine. Events causing chromosomal abnormalities in ESCs may be related to events in tumor cells causing chromosomal instability (CIN) in human disease. However, the underlying mechanisms are unknown. Using multiparametric permeabilized-cell flow cytometric analysis, we found that the mitotic-spindle checkpoint, which helps maintain chromosomal integrity during all cell divisions, functions in human and mouse ESCs, but does not initiate apoptosis as it does in somatic cells. This allows an unusual tolerance to polyploidy resulting from failed mitosis, which is common in rapidly proliferating cell populations and which is reduced to near-diploid aneuploidy, which is also common in human neoplastic disease. Checkpoint activation in ESC-derived early-differentiated cells results in robust apoptosis without polyploidy/aneuploidy similar to that in somatic cells. Thus, the spindle checkpoint is “uncoupled” from apoptosis in ESCs and is a likely source of karyotypic abnormalities. This natural behavior of ESCs to tolerate/survive varying degrees of ploidy change could complicate genome-reprogramming studies and stem-cell plasticity studies, but could also reveal clues about the mechanisms of CIN in human tumors.

Karyotypic abnormalities in cultured embryonic stem cells (ESCs), especially near-diploid aneuploidy, are potential obstacles to ESC use in regenerative medicine. Events causing chromosomal abnormalities in ESCs may be related to events in tumor cells causing chromosomal instability (CIN) in human disease. However, the underlying mechanisms are unknown. Using multiparametric permeabilized-cell flow cytometric analysis, we found that the mitotic-spindle checkpoint, which helps maintain chromosomal integrity during all cell divisions, functions in human and mouse ESCs, but does not initiate apoptosis as it does in somatic cells. This allows an unusual tolerance to polyploidy resulting from failed mitosis, which is common in rapidly proliferating cell populations and which is reduced to near-diploid aneuploidy, which is also common in human neoplastic disease. Checkpoint activation in ESC-derived early-differentiated cells results in robust apoptosis without polyploidy/aneuploidy similar to that in somatic cells. Thus, the spindle checkpoint is “uncoupled” from apoptosis in ESCs and is a likely source of karyotypic abnormalities. This natural behavior of ESCs to tolerate/survive varying degrees of ploidy change could complicate genome-reprogramming studies and stem-cell plasticity studies, but could also reveal clues about the mechanisms of CIN in human tumors.

The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A polymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3A gene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3A or FCGR2A alleles. The FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.

The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3Aand FCGR2Agene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3Avaline (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P= .002), while no difference was found between FCGR2Apolymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3Agene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3Aor FCGR2Aalleles. The FCGR3Asingle nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.

The regulatory mechanisms for the proliferation and the particular invasive phenotypes of stomach cancers are not still fully understood. Up-regulations of hepatocytes growth factor (HGF), its receptor (c-Met), and urokinase-type plasminogen activator (uPA) are correlated with the development and metastasis of cancers. In order to investigate roles of HGF/c-Met signaling in tumor progression and metastasis in stomach cancers, we determined effects of a specific MEK1 inhibitor (PD098059) and a p38 kinase inhibitor (SB203580) on HGF-mediated cell proliferation and uPA expression in stomach cancer cell lines (NUGC-3 and MKN-28). HGF treatment induced the phosphorylations of ERK and p38 kinase in time- and dose- dependent manners. Pre-treatment with PD098059 reduced HGF-mediated cell proliferation and uPA secretion. In contrast, SB203580 pre-treatment enhanced cell proliferation and uPA secretion due to induction of ERK phosphorylation. Stable expression of dominant negative-MEK1 in NUGC-3 cells showed a decrease in HGF-mediated uPA secretion. These results suggest that interaction of a MEK/ERK and a p38 kinase might play an important role in proliferation and invasiveness of stomach cancer cells.

Nikkomycin Z is a competitive inhibitor of chitin synthases in fungi. It has been reported that it inhibits chitin synthases (Chs) 1 and 3, but not 2, of Saccharomyces cerevisiae. In our study, we found that: (a) nikkomycin Z inhibited all three Chs isozymes of Candida albicans(CaChs). The IC50value for CaChs1 is 15 µM, for CaChs2 0.8 µM, and for CaChs3 13 µM; (b) nikkomycin Z inhibits vegetative growth of C. albicansdifferently in different growth media; growth inhibition was observed on Spider and corn meal agar plate, but not on Lee's plate; (c) growth inhibition by nikkomycin Z accompanied by the absence of septum and cell wall chitin, which in turn brought about cell lysis. Nikkomycin Z did not lyse cells in Lee's media and lysis was partially prevented in the presence of sorbitol as an osmostabilizer in Spider medium. Therefore, nikkomycin Z prevented the formation of septum and cell wall chitin by inhibiting chitin synthase activities in a growth medium‐dependent manner. Copyright © 2002 John Wiley & Sons, Ltd.

Myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) is a central nervous system inflammatory disorder associated with MOG antibodies. Two patients with clinical symptoms of cauda equina syndrome had positive serum MOG antibody tests, and spinal magnetic resonance imaging showed cauda equina enhancement. They were diagnosed with incomplete cauda equina syndrome associated with MOGAD. A few cases of lumbosacral radiculomyelitis associated with MOGAD have been reported; however, this is the first report of isolated lumbosacral radiculitis associated with MOGAD without transverse myelitis. The MOG antibody test should be considered for cauda equina syndrome without compressive lesions.

Yoon: Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kyowa Hako Kirin: Research Funding; Janssen: Consultancy; Yuhan Pharma: Research Funding; Genentech, Inc.: Research Funding; MSD: Consultancy.

Yoon: Genentech, Inc.: Research Funding; MSD: Consultancy; Yuhan Pharma: Research Funding; Janssen: Consultancy; Novartis: Consultancy, Honoraria; Kyowa Hako Kirin: Research Funding; Amgen: Consultancy, Honoraria. Yoon:F. Hoffmann-La Roche Ltd: Research Funding.

Background: Transplant-ineligible Patients with relapsed/refractory multiple myeloma (RRMM) who failed both proteasome inhibitors and immunomodulators have a short life expectancy. Accordingly, effective third- or later-line therapy is needed for improving survival outcomes. Therefore, we planned to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCD) in elderly patients with RRMM who had failed both bortezomib and lenalidomide.

Background

Yoon: Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy, Honoraria; Yuhan Pharma: Research Funding; Amgen: Consultancy, Honoraria; Genentech, Inc.: Research Funding; Kyowa Hako Kirin: Research Funding. Kim:F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding.

Introduction

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.